Immune-based Therapy Pilot Study for the Treatment of Primary HIV Infection (PHI-IMD). (PHI-IMD)

Immune-based Therapy Pilot Study for the Treatment of Primary HIV Infection With the Objective to Induce a Strong Specific HIV Immune Response Able to Control Viral Replication Without Highly Active Anti-Retroviral Therapy (HAART)

Pilot study for the treatment of primary HIV infection with the objective to induce a strong specific HIV immune response able to control viral replication without HAART.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: HAART; Drug: HAART + Immunotherapy

Detailed Description

Pilot and open RCT in 20 patients with primary HIV-1 infection who were randomized to one of these two arms: 1) Control arm (A), Tenofovir +Lamivudine + Lopinavir-ritonavir (Kaletra) at standard doses for 44 weeks (W44); a short treatment interruption (TI) was performed at W36, and HAART was restarted for 8 weeks when plasma HIV-1 RNA viral load (pVL) rebounded>200 copies/mL. At W44 HAART was stopped and patients were followed for 48 additional weeks (W92). 2) Immune-based arm (B), same HAART schedule plus oral cyclosporine A (CsA)(serum levels 250-350 mcg/L) for the first 8 weeks of HAART. During the TI, patients received sc GM-CSF (250 mcg TIW) plus weekly sc pegylated-interferon a2b (Peg-INF)(1.5 mcg/kg/week). During the last 8 weeks of HAART (until W44), patients received daily sc low-dose interleukin-2 (IL-2)(0.75 MU/kg QD). The primary endpoint was pVL <1000copies/mL (<3.0 log10/mL) at 12 (W56) and at 48 (W92) weeks after stopping HAART. Sample size was calculated in order to detect a pVL difference of 1.5log10 copies/mL at 12 (W56) weeks after stopping HAART between the control and the immune-based arms with a power of 80% and a level of significance of0.05.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HIV-infected patients (age 18 years or over) with primary HIV infection <90 days.
2. Giving written informed consent to participate into the study.

Exclusion Criteria:

1. Patients not accepting to start HAART. Patients wishing start HAART treatment with nevirapine or efavirenz.
2. Pregnant women or planning pregnancy.
3. Intravenous drug user or alcohol abuse.
4. Previous treatment with cyclosporin A, GM-CSF,pegylated-interferon-alpha o interleukine-2.
5. Renal or liver failure.
6. Any formal contraindication to treatment with the study drugs.
7. Patients with a history of psychiatric disorder, thyroid illness, dislipidemia requiring treatment, cardiovascular disease, arterial hypertension, or diabetes mellitus.
8. In treatment with drugs interacting with study drugs.
9. Acute infection for HTLV-I or EBV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HAART; Patients assigned to this arm will receive standard HAART	Drug: HAART; Patients assigned to this arm will receive Trizivir and kaletra. After the first 9 months of HAART, all patients will stop HAART until HIV viral load in plasma became detectable (>200 copies/mL). Then, they will re-start HAART plus low doses of IL-2 during 2 months. All patients will be followed-up during 1 year.; Other Names: Viread; Kaletra; Epivir
Experimental: HAART + Immunotherapy; Patients assigned to this arm will receive HAART plus cyclosporin A during the first two months and after that will receive IFN, GM-CSF and IL-2.	Drug: HAART + Immunotherapy; Patients assigned to this arm will receive Trizivir + Kaletra + cyclosporin A during the first two months. This group also will receive GM-CSF plus pegylated-interferon-alpha until HIV viral load in plasma became detectable (>200 copies/mL). Then, they will re-start HAART plus low doses of IL-2 during 2 months. At this moment they will stop HAART. All patients will be followed-up during 1 year.; Other Names: Interleukin-2; GM-CSF; Cyclosporine A; Peg-IFN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients remaining below 5,000 copies/mL at 12 and 48 weeks after stoping HAART.	W12 y W48

Secondary Outcome Measures

Outcome Measure	Time Frame
Adherence to treatment	W8, W24, W36, W96
CD4, CD8	W8, W24, W36, W96
Specific HIV immune responses (CD4 and CTL)	W8, W24, W36, W96
Proportion of patients PVL (plasma viral load)<40	W8, W24, W36, W96
Adverse events	W8, W24, W36, W96

Collaborators and Investigators

• Sponsor: Juan A. Arnaiz
• Investigators: Principal Investigator: Josep Maria Miró, MDPhD, Hospital Clinic of Barcelona

Publications and helpful links

General Publications

• Nicolas D, Ambrosioni J, Sued O, Brunet M, Lopez-Dieguez M, Manzardo C, Aguero F, Tuset M, Plana M, Guardo AC, Mosquera MM, Munoz-Fernandez MA, Caballero M, Marcos MA, Gatell JM, de Lazzari E, Gallart T, Miro JM. Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial. J Antimicrob Chemother. 2017 Mar 1;72(3):829-836. doi: 10.1093/jac/dkw462.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: September 16, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimate): September 18, 2009

Study Record Updates

• Last Update Posted (Estimate): November 19, 2014
• Last Update Submitted That Met QC Criteria: November 18, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Interleukin-2
• Other Study ID Numbers: PHI-INMUNOMEDIADO